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Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway

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Tumor Biology

Abstract

Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

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References

  1. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis. 2007;28:233–9.

    Article  CAS  PubMed  Google Scholar 

  2. Ismail T, Sestili P, Akhtar S. Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. J Ethnopharmacol. 2012;143:397–405.

    Article  CAS  PubMed  Google Scholar 

  3. Karasu C, Cumaoglu A, Gurpinar AR, Kartal M, Kovacikova L, Milackova I, et al. Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts. Interdiscip Toxicol. 2012;5:15–20.

    Article  PubMed  PubMed Central  Google Scholar 

  4. El Kar C, Ferchichi A, Attia F, Bouajila J. Pomegranate (Punica granatum) juices: chemical composition, micronutrient cations, and antioxidant capacity. J Food Sci. 2011;76:C795–800.

    Article  PubMed  Google Scholar 

  5. Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005;16:360–7.

    Article  CAS  PubMed  Google Scholar 

  6. Cacioppo JT, Cacioppo S. Social relationships and health: the toxic effects of perceived social isolation. Soc Personal Psychol Compass. 2014;8(2):58–72.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dhabhar FS. A hassle a day may keep the pathogens away: the fight-or-flight stress response and the augmentation of immune function. Integr Comp Biol. 2009;49:215–36.

    Article  CAS  PubMed  Google Scholar 

  8. Thaker PH, Lutgendorf SK, Sood AK. The neuroendocrine impact of chronic stress on cancer. Cell Cycle. 2007;6:430–3.

    Article  CAS  PubMed  Google Scholar 

  9. Zafir A, Banu N. Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress. 2009;12:167–77.

    Article  CAS  PubMed  Google Scholar 

  10. Suhail N, Bilal N, Hasan S, Ahmad A, Ashraf GM, Banu N. Chronic unpredictable stress enhances the carcinogenic potential of 7,12-dimethyl benz (a) anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice. Cell Stress Chaperones. 2015;20(6):1023–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Oritz J, Fitzgerald IW, Lane S, Terwilliger R, Nestler EJ. Biochemical adaptations in the mesolimbic dopamine system in response to repeated stress. Neuropschyopharmacology. 1996;14:443–52.

    Article  Google Scholar 

  12. Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–10.

    Article  Google Scholar 

  13. Jollow DJ, Mitchell JR, Zampaglione N, Gillete JR. Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3, 4, bromobenzene oxide as the hepatotoxic intermediate. Pharmacology. 1974;11:151–69.

    Article  CAS  PubMed  Google Scholar 

  14. Marklund S, Marklund G. The involvement of the superoxide anion radical in the auto oxidation of Pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:469–74.

    Article  CAS  PubMed  Google Scholar 

  15. Claiborne A. Catalase activity. In: Green Wald RA, editor. CRC handbook of methods for oxygen radical research. Boca Raton: CRC Press; 1985. p. 283–4.

    Google Scholar 

  16. Habig W, Pabst MJ, Jacoby WH. Glutathione-s-transferases: the first step in mercapturic acid formation. J Biol Chem. 1994;249:7130–9.

    Google Scholar 

  17. Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975;250:5475–80.

    CAS  PubMed  Google Scholar 

  18. Lowry OH, Rosenberg NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem. 1951;193:265–75.

    CAS  PubMed  Google Scholar 

  19. Pool-Zobel BL, Guigas C, Klein RG, Neudecker CH, Renner HW, Schnezer P. Assessment of genotoxic effect by lindane. Food Chem Toxicol. 1993;31:271–83.

    Article  CAS  PubMed  Google Scholar 

  20. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184–91.

    Article  CAS  PubMed  Google Scholar 

  21. Muqbil I, Azmi AS, Banu N. Prior exposure to restraint stress enhances 7, 12-dimethylbenz(a)anthracene (DMBA) induced DNA damage in rats. FEBS Lett. 2006;580:3995–9.

    Article  CAS  PubMed  Google Scholar 

  22. Yang Y, Karakhanova S, Werner J, Bazhin AV. Reactive oxygen species in cancer biology and anticancer therapy. Curr Med Chem. 2013;20:3677–92.

    Article  CAS  PubMed  Google Scholar 

  23. Davies KJ, Sevanian A, Muakkassah-Kelly SF, Hochstein P. Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid. Biochem J. 1986;235:747–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yildirim NC, Kandemir FM, Ceribasi S, Ozkaraca M, Benzer F. Pomegranate seed extract attenuates chemotherapy-induced liver damage in an experimental model of rabbits. Cell Mol Biol (Noisy-le-grand). 2013;59Suppl:OL1842–7.

  25. Kaur G, Jabbar Z, Athar M, Alam MS. Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem Toxicol. 2006;44:984–93.

    Article  CAS  PubMed  Google Scholar 

  26. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000;71:1062–76.

    CAS  PubMed  Google Scholar 

  27. Sutherland BM, Bennett PV, Georgakilas AG, Sutherland JC. Evaluation of number average length analysis in quantifying double strand breaks in genomic DNAs. Biochemistry. 2003;42:3375–84.

    Article  CAS  PubMed  Google Scholar 

  28. Hasan S, Fatima N, Bilal N, Suhail N, Fatima S, Morgan EN, et al. Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation. Appetite. 2013;65:68–74.

    Article  PubMed  Google Scholar 

  29. Vineis P, Pursianinen KH. Air pollution and cancer: biomarker studies in human populations. Carcinogenesis. 2005;26:1846–55.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Aligarh Muslim University, Aligarh, for providing necessary facilities. The financial assistance in the form of a scholarship to the authors from the University Grants Commission (UGC), New Delhi, is thankfully acknowledged.

Author information

Author notes

  1. Shirin Hasan

    Present address: Department of Surgery, Loyola University Chicago, Maywood, IL, USA

  2. Naheed Banu

    Present address: College of Medical Rehabilitation, Qassim University, P.O. Box 2100, Buraydah, 51451, Saudi Arabia

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, Uttar Pradesh, India

    Shirin Hasan, Nida Suhail, Nayeem Bilal, Ghulam Md. Ashraf & Naheed Banu

  2. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

    Syed Kashif Zaidi

  3. Department of Family and Community Medicine, College of Medicine, Qassim University, Qassim, Saudi Arabia

    Sultan AlNohair

  4. Department of Biochemistry, Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia

    Nida Suhail

  5. King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Saudi Arabia

    Ghulam Md. Ashraf

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  1. Shirin Hasan
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Correspondence to Naheed Banu.

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Hasan, S., Suhail, N., Bilal, N. et al. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway. Tumor Biol. 37, 5999–6006 (2016). https://doi.org/10.1007/s13277-015-4469-9

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  • DOI: https://doi.org/10.1007/s13277-015-4469-9

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